The harmful effects of radiation, chemotherapeutic drugs, and other chemicals on spermatogenic cells will be examined. The effects to be considered are killing of stem cells which could result in sterility and alterations in the DNA which could produce genetic mutations. Quantitative measurements of mouse testicular stem cell survival will be performed by histological methods, measurement of LDH-X enzyme activity, and sperm counts. Additional chemicals, dose regimes, and combinations of chemicals will be tested by these methods. The hypothesis that measurements of stem cell survival are sufficient to predict the eventual return to fertility will be tested by measuring these parameters with several different cytotoxic treatments. Biochemical alterations in DNA produced by radiation or drugs will be assayed in mouse testicular cells at specific stages of spermatogenesis. DNA damage will be assayed by measuring strand breaks, or alkylations. DNA repair will be measured by unscheduled DNA synthesis. Alterations in DNA content of individual mouse spermatids or sperm will be determined by flow cytometry. Sperm in human semen ejaculates from cancer patients who have received chemotherapy will be analyzed. Sperm counts will be performed prior to and at selected intervals following chemotherapy in order to determine whether the treatment has a sterilizing effect and the time course of the return to fertility. In a collaborative study, morphological sperm abnormalities will be scored in order to determine whether this parameter could detect genetic mutations resulting from chemotherapy regimes. Possible mutations will also be analyzed by flow cytometry and sperm karyotyping by fusion with hamster ova.